The general aim of this proposal is to optimize the imaging techniques used to study airway physiology in the lungs of patients with cystic fibrosis (CF). Deficiencies in mucociliary clearance (MCC), a primary airway host defense mechanism, make patients with CF more vulnerable to chronic and ultimately life threatening infections. Further development of the imaging techniques that quantify MCC and the underlying pathophysiology of CF will increase their utility as outcome measures, allowing for the accelerated evaluation of treatments that will ultimately extend the survival of this population. The research portion of the proposal includes the development of a 2-isotope nuclear medicine scan to simultaneously assess mucociliary clearance rate and airway surface liquid volume. This is an extension of the single isotope technique previously used by the investigators to study MCC in this population. Manual and automated quantitative computed tomography (CT) techniques will also be utilized, allowing regional differences in clearance rate to be matched to specific pathologies within the lungs and localized to airways within specific size ranges. The design of a new system for more precise, repeatable, and targeted delivery of the aerosols used to assess pulmonary clearance is also proposed. Career development proposed during the award includes: (1) on going research training in CF, (2) the mentored study of advanced nuclear medicine techniques, (3) instruction in CT image quantification, (4) a graduate course in the Foundations of Biomedical Science, (5) an on-going consultation with researchers at the University of North Carolina who are pursuing similar research interests, (6) continued participation in Gordon Conferences on cilia, mucus, and mucociliary interactions, and (7) monthly instruction from a thoracic radiologist to learn CT scan interpretation. The proposed research and training will provide the core skills necessary to progress towards research independence in a field at a unique interface between engineering and medicine. (End of Abstract)